IC4 VTE Flashcards
Virchow’s Triad
- Hypercoagulability
- Vascular damage / vessel injury
- Circulatory / venous stasis
Examples of risk factors based on Virchow’s Triad
Hypercoagulability
- Inflammation (release of hypercoagulable chemicals)
- Estrogen, Tamoxifen
- Dehydration
- Infection and sepsis
- Protein C and S deficiency
- Factor VIII, XI excess
- APS antibodies
- Pregnancy + up to 6w post partum
Vascular damage
- Thrombophlebitis
- Cellulitis
- Atherosclerosis
- Trauma
- Venous catheters
Circulatory Stasis
- Immobility
- Surgery
- Polycythemia
- Venous obstruction (obesity, tumor, pregnancy)
- AFib
- Congenital abnormalities affecting venous anatomy
- Bradycardia
- Low BP
Distal VS Proximal DVT
- List the veins involved
Distal:
- Peroneal, anterior tibial, posterior tibial veins
Proximal:
- popliteal, femoral, iliac veins
- more likely to embolise (IVC => right heart => PE)
Explain how PE might lead to circulatory collapse
PE can result in occlusion of blood flow to lung => impaired gaseous exchange => necrosis => impaired O2 delivery to other organs => fatal circulatory collapse
Infarction of lung tissue => back damming into heart => right ventricle failure => left ventricle failure
S&S of DVT
Differential diagnosis
Symptoms:
- Leg swelling, pain, warmth (non-specific, hence require testing)
- Unilateral
- May present with fever
Signs:
- Palpable cord in leg (dilated superficial vein)
- Homan’s sign - pain in the back of the knee when foot is flexed
*Differential diagnosis:
- cellulitis (CUS to identify clots)
- HF: fluid overload (bilateral)
S&S of PE
Differential diagnosis
(Usually underlying DVT)
Symptoms:
- Cough, chest pain, chest tightness, SOB, palpitation, hemoptysis, pleural effusion
- Dizziness, light-headedness (due to poor perfusion, circulatory collapse)
Signs:
- Tachypnea, tachycardia, diaphoretic (sweating)
- Neck vein distended
- Cyanotic, hypotensive
- Oxymetry: hypoxic
- Cardiogenic shock
*Differential diagnosis:
- MI (both MI and PE can present with ECG changes)
Explain the patho of hemoptysis and pleuritic chest pain in PE
Small distal emboli can create areas of alveolar hemorrhage, thus leading to hemoptysis, pleuritis, pleuritic chest pain, pleural effusion
DVT diagnosis
- Wells-DVT Score
- If >2 points, imaging with whole leg or proximal CUS
- If 0-2 points, perform D-dimer (if D-dimer positive –> imaging)
- Distal DVT –> anticoagulation or surveillance
- Proximal DVT –> initiate anticogulation
[DVT diagnosis]
Other investigations to exclude differential diagnosis
- FBC rule out infection (although blood shift can occur in DVT/PE, total whites can incr in MI)
- Procalcitonin - rule out infection
- Renal panel
- NT-proBNP - rule out HF
D-dimer is a by-product of?
Degradation of fibrin mesh (when plasmin cleaves fibrin)
[DVT diagnosis]
Explain the utility of D-dimer
What are some other conditions that can raise D-dimer?
Good negative predictive value (pre-test probability, rule-in rule-out)
- If negative –> can rule out DVT
- If positive –> cannot confirm DVT
Other conditions that can raise D-dimer:
- pregnancy
- malignancy
- pneumonia
- heart failure
- post-surgery
[DVT diagnosis]
Well’s score:
1 point each:
- Active cancer (ongoing tx or within previous 6m)
- Paralysis/paresis/immobilization of lower extremities
- Recently bedridden for >3 days or major surgery within 4 weeks
- Localized tenderness
- Entire leg swollen
- Calf swelling by more than 3cm (measured 10cm below tibial tuberosity)
- Pitting edema
- Collateral superficial veins (non varicose)
High probability: 3 and above
Mod probability: 1-2
Low probability: 0
=> DVT likely: 2 or greater
=> DVT unlikely: 1 or less
[VTE treatment]
Acute treatment of VTE
- Key principles
- Thrombolytic therapy is only considered in pt with severe cardiopulmonary compromise or DVT with high risk of limb loss, thrombolytic therapy must be followed by anticoagulation with UFH or LMWH
- If pt has active bleeding, unable to use anticoagulation, AND VTE is in lower extremity, consider IVC filter
- If pt is suitable for outpatient VTE tx (no active bleeding, no PE, not CI w anticoagulants), consider: DOAC/LMWH/Warfarin
- If pt is unsuitable for outpatient VTE tx (e.g., due to poor prognosis), consider: DOAC/LMWH/UFH/Warfarin
- If pt is unsuitable for outpatient VTE tx and CrCl <30ml/min, consider: UFH x5d with Warfarin overlap
[VTE treatment]
- Apixaban
Apixaban 10mg BD x7d, followed by 5mg BD for 3-6months
Extended: 2.5mg BD
Preferred as it is subsidized (SDL2), however, less convenient than Riva due to twice daily dosing
[VTE treatment]
- Rivaroxaban
Rivaroxaban 15mg BD x21d, followed by 20mg OD for 3-6m
Extended: 10mg OD
[VTE treatment]
- Dabigatran/Edoxaban
UFN/LMWH/fondaparinux (subQ) for first 5d,
followed by Dabigatran 150mg BD or Edoxaban 60mg OD
*LMWH first line, unless CrCl <30 then use UFH
[VTE treatment]
- Warfarin
UFN/LMWH/fondaparinux (subQ) for at least 5 days,
OVERLAP w Warfarin daily, INR range 2-3
*LMWH first line, unless CrCl <30 then use UFH
[VTE treatment]
Explain difference between transient and chronic risk factors
How does this affect duration of VTE treatment?
Transient/Provoked: e.g., traffic accident, recent surgery
Chronic/unprovoked: antiphospholipid syndrome (APS), hereditary thrombophilia
Transient - 3months
Chronic - typically extend beyond 3m
- First unprovoked isolated distal DVT - at least 3 months
- First unprovoked proximal DVT/PE - at least 3 months, consider 6 months (if bleeding risk acceptable, follow up once a year)
*In pt stopping anticoagulation, consider low dose aspirin
[VTE treatment]
Recommendation for severe renal impairment CrCl <30ml/min
Do not use DOACs
Use UFH/LMWH + Warfarin overlap
UFH + Warfarin is preferred
If use LMWH - must be dose reduced enoxaparin
LMWH => renally excreted, accumulates in renal failure, ma incr risk of major bleeding
UFH => minimal renal excretion, short half-life
[VTE treatment]
UFH vs LMWH (Enoxaparin)
Dosing of Enoxaparin
IV UFH
subQ enoxaparin preferred
- dosed by body weight: 1mg/kg q12h OR 1.5mg/kg q24h
- In CrCl <30ml/min, use 1mg/kg q24h
- Enoxaparin (Clexane) comes in 20mg/0.2ml, 40mg/0.4ml, 60mg/0.6ml (graduated), 80mg/0.8ml (graduated)
[VTE treatment]
Compare protein binding of anticoagulants used in VTE tx
DRAW
Dabigatran (most renally cleared)
Rivaroxaban
Apixaban
Warfarin (highest protein binding, most hepatically cleared)
Edoxaban is minimally hepatically and renally cleared
[VTE Prophylaxis]
Algorithm
- Risk factors for VTE
- If high risk for VTE, consider pharmacologic prophylaxis or pneumatic compression device (depending on bleeding risk)
- If low risk for VTE, VTE prophylaxis not indicated
[VTE Prophylaxis]
3 main high risk groups that require VTE prophylaxis
- Medically ill (e.g., severe sepsis, heart failure, prolonged immobility, thrombophilia)
- Surgical patients (e.g., hip replacement surgery, knee replacement)
- Cancer patient
[VTE Prophylaxis]
- Dosing of enoxaparin
*SC Enoxaparin preferred to SC UFH
No longer by body weight (like in VTE tx or PCI), flat dose of 40mg once daily
THR/HFS: 40mg OD or 30mg BD
Duration for surgical indications: 10-14d, up 35d
Because LMWH is renally excreted, dose adjustment needed in renal impairment:
- CrCl 30-50ml/min - 30mg q12h
- CrCl <30ml/min - 20-30mg once daily
NOTE THAT:
- Bariatric surgery (for obese pt) - VTEP dose is different (BMI >=40: 40mg BD, BMI >50: 60mg BD)
[VTE Prophylaxis]
- DOAC doses
Apixaban 2.5mg BD
- Start within 12-24h post-surgery, provided hemostasis achieved
- 10-14d TKR; 32-35d THR
Rivaroxaban 10mg OD
- Start within 6-10h post-surgery, provided hemostasis achieved
- 14d for TKR, 35d for THR
- Medically ill up 31-39days
Edoxaban 30mg/day
Dabigatran 220mg/day
- start within 1-4h post-surgery, provided hemostasis achieved
- 10d (TKR), 28-53d (THR)
- CrCl 30-50ml/min: use 150mg OM
[VTE tx/prophylaxis]
DOAC renal adjustments
Apixaban
- CrCl 15-29ml/min: use with caution
- HD: avoid
Rivaroxaban
- CrCl <30ml/min: avoid use
Edoxaban
- CrCl 30-50ml/min OR BW =<60kg: 30mg/day (instead of 60mg/day)
- CrCl >95ml/min: avoid use
Dabigatran (recall most renally cleared)
- CrCl <50ml/min + concomitant PgP inhibitors: avoid
IN GENERAL,
avoid use when CrCl <30ml/min
for Dabi <50ml/min,
for edoxaban half dose when 30-50ml/min
Risk factors for DVT recurrence after first episode of unprovoked VTE
=> therefore consider need for anticoagulation
- Proximal DVT location
- Obesity
- Old age
- Early prothrombotic phlebitic syndrome (PTS) development
- High D-dimer values
- Role of inherited thrombophilia (?)
- Persistence of residual vein thrombosis at ultrasound
- Male sex
- Non-zero blood group
PE diagnosis algorithm
- Wells score
- If >4: imaging (CTPA - pulmonary angiogram, VQ scan - ventilation-perfusion scan)
- If 4 or less: D-dimer (if positive –> imaging)
- Positive imaging: initiate anticoagulant
[PE diagnosis]
Well’s score
- Clinical symptoms of DVT (leg swelling, pain with palpation) [3]
- Other diagnosis less likely than pulmonary embolism [3]
- HR >100 [1.5]
- Immobilization (>=3 days) or surgery in previous 4 weeks [1.5]
- Previous DVT/PE [1.5]
- Hemoptysis [1]
- Malignancy [1]
High probability: >6
Mod probability: 2-6
Low probability: <2
=> PE likely >4
=> PE unlikely =<4
[PE diagnosis]
Indicators of risk (high/intermediate/low)
- Hemodynamic instability (look at BP - hypotensive, shock)
- Clinical parameters of PE severity and/or comorbidity
- RV dysfunction (congestion) on TTE or CTPA
- Elevated cardiac troponin levels
=> Basically, require:
- TTE
- CTPA
- BP
- Cardiac troponin level
[PE diagnosis]
Acute high risk PE
- Clinical manifestations
Haemodynamic instability:
- Cardiac arrest (need for cardiopulmonary resuscitation)
- Obstructive shock (systolic BP <90mmHg or vasopressors required AND end-organ hypoperfusion)
- Persistent hypotension (systolic BP <90mmHg, or systolic BP drop >=40mmHg, lasting longer than 15min)
*rTPA and UFH indicated for high risk PE
[PE treatment]
Acute high risk PE
- treatment
- Recommended to use UFH (weight-adjusted bolus injection) as anticoagulant (because UFH has minimal renal excretion + short half-life, therefore easily reversible)
- Recommended to start systemic thrombolytic (Alteplase) as high risk of mortality outweighs risks of bleeding
- Recommend surgical pulmonary embolectomy or Percutaneous catheter-directed treatment can be considered for pt with high risk PE whom thrombolytic is contraindicated/failed
- Supportive management such as fluid replacement, inotropes should be considered for hemodynamic instability
[PE treatment]
Alteplase dosing and administration
Used for thrombolysis in PE/DVT/AIS
- Dose by body weight
- Via infusion
- require follow up and monitoring for bleeding processes, BP control, critical to avoid hemorrhagic conversion
Compared to Tenecteplase - used in AMI, dosed by body weight via single IV bolus (easier dosing and administration)
[PE treatment]
Intermediate-low risk PE
- treatment
- Recommended to initiate parenteral LMWH/fondaparinux over UFH, OR, oral NOAC over VKA
- If VKA used, need to overlap with LMWH till INR 2-3
- NOAC not recommended if CrCl <30ml/min, pregnancy, lactation, antiphospholipid syndrome
- VKA recommended in APS
- Use of thrombolytic not recommended
[PE treatment]
In the event pt needs to be switched from LMWH/DOAC to thrombolytic (due to deterioration while on the anticoagulant), what are the time intervals to take note?
LMWH to thrombolytics (should not be within 24h of LMWH administration)
DOAC to thrombolytic (hold DOAC 48h before thrombolytic administration)
[PE treatment]
Contraindications to use of thrombolytics
- Absolute
- Relative
Absolute:
- Hx of hemorrhagic stroke
- Ischemic stroke in last 6m
- CNS neoplasm
- Major trauma/surgery/head injury in past 3w
- Bleeding diathesis
- Active bleeding
Relative:
- TIA in past 6m
- Oral anticoagulation
- Pregnancy, first post-partum week
- Non-compressible puncture sites
- Traumatic resuscitation
- Refractory HTN (SBP >180mmHg) - incr risk of hemorrhagic conversion
- Advanced liver disease
- Infective endocarditis
- Active peptic ulcer
[PE treatment]
Dose and Duration
Follow up monitoring
Similar to DVT treatment
Transient (first VTE with a major transient/reversible risk factor): 3 months
Chronic (recurrent VTE without major transient or reversible risk factor): extension beyond 3 months
Follow up:
- Drug tolerance, adherence
- Monitor hepatic and renal function
- S&S of bleeding and recurrent VTE
[DVT/PE in pregnancy]
- Diagnosis
- Suspected PE during pregnancy
High pretest probability OR intermediate-low probability and positive D-dimer result => commence anticoagulation with LMWH - CXR to assess PE, and CUS to assess proximal DVT
- If proximal DVT not present, perform CTPA to evaluate PE
- If DVT or PE present => continue LMWH at therapeutic dose
[DVT/PE in pregnancy]
- Treatment agent
LMWH at therapeutic dose
- dosed by weight (subQ 1mg/kg q12h)
- DO NOT use DOAC/Warfarin in pregnancy and lactation
[DVT/PE in pregnancy]
- Young females with hist of thrombosis and spontaneous abortions should be worked up for _____
- Tx OAC choice for these patients?
Antiphospholipid syndrome (APS)
- Determines anticoagulation choice post-partum
- Cannot use warfarin/DOAC during pregnancy, use LMWH
- Post-partum: switch back to VKA
